Codon 72 is a hotspot of polymorphisms in the TP53 gene, which encodes a hub protein in the protein–protein interaction network of p53. It is thus a central player in the apoptotic pathway, preventing cancer. A large number of articles have been published exploring its association with an increased susceptibility to most common cancers. However, these studies have produced inconclusive results, which may be due to their small sample sizes or study designs. To comprehensively evaluate the potential correlation between the TP53 Pro72Arg polymorphism and cancer risk and to better characterize the Pro72Arg polymorphism, we performed a systematic HuGE review and meta-analysis of candidate studies through online resources, according to the proposal of MOOSE and the PRISMA statement. The identified articles were carefully examined according to the inclusion criteria. Pooled odds ratios were calculated on the basis of different genetic models, while heterogeneity was assessed through a chi-based Q-test and I2. After applying the inclusion filters, we obtained a pool of 54 eligible studies, representing 18 718 cases and 21 261 controls. Overall, non-significant cancer risk was observed in all the genetic models but their observed heterogeneity was extremely significant. In subgroup analysis, an increased susceptibility was observed in the case of colorectal cancer, while in cancers of the female reproductive system, significantly increased risk was detected in all the genetic models except the dominant model. In another subgroup analysis, significantly increased cancer risk was observed among Asians in homozygous and recessive models, while in Americans increased cancer risk was observed only in dominant and recessive models. No association was observed in the rest of the populations. In conclusion, pooled subgroup analysis on the basis of ethnicity proved that the TP53 Arg72Pro polymorphism is associated with an increased risk of cancer in Asians and Americans only and is not associated in other populations. It can therefore be concluded that this meta-analysis of available data suggests partial confirmation of the association between the TP53 Arg72Pro polymorphism and cancer risk susceptibility.

Studies of complex genetic diseases have revealed many risk factors of small effect, but the combined amount of heritability explained is still low. Genome-wide association studies are often underpowered to identify true effects because of the very large number of parallel tests. There is, therefore, a great need to generate data sets that are enriched for those markers that have an increased a priori chance of being functional, such as markers in genomic regions involved in gene regulation. ReMo-SNPs is a computational program developed to aid researchers in the process of selecting functional SNPs for association analyses in user-specified regions and/or motifs genome-wide. The useful feature of automatic selection of genotyped markers in the user-provided material makes the output data ready to be used in a following association study. In this article we describe the program and its functions. We also validate the program by including an example study on three different transcription factors and results from an association study on two psychiatric phenotypes. The flexibility of the ReMo-SNPs program enables the user to study any region or sequence of interest, without limitation to transcription factor binding regions and motifs. The program is freely available at: http://www.neuro.ki.se/ReMo-SNPs/

An understanding of the perceived importance of a variety of factors affecting the ease of handling of sheep and the interactions between these factors is valuable in improving profitability and welfare of the livestock. Many factors may contribute to animal behaviour during handling, and traditionally these factors have been assessed in isolation under experimental conditions. A human social component to this phenomenon also exists. The aim of this study was to gain a deeper understanding of the importance of a variety of factors affecting ease of handling, and the interactions between these from the perspective of the livestock transporter. Qualitative interviews were used to investigate the factors affecting sheep behaviour during handling. Interview transcripts underwent thematic analysis. Livestock transporters discussed the effects of attitudes and behaviours towards sheep, helpers, facilities, distractions, environment, dogs and a variety of sheep factors including breed, preparation, experience and sex on sheep behaviour during handling. Transporters demonstrated care and empathy and stated that patience and experience were key factors determining how a person might deal with difficult sheep. Livestock transporters strongly believed facilities (ramps and yards) had the greatest impact, followed by sheep experience (naivety of the sheep to handling and transport) and breed. Transporters also discussed the effects of distractions, time of day, weather, dogs, other people, sheep preparation, body condition and sheep sex on ease of handling. The concept of individual sheep temperament was indirectly expressed.

Intramuscular fat (IMF) % contributes positively to the juiciness and flavour of lamb and is therefore a useful indicator of eating quality. A rapid, non-destructive method of IMF determination like computed tomography (CT) would enable pre-sorting of carcasses based on IMF% and potential eating quality. Given the loin muscle (longissimus lumborum) is easy to sample, a single measurement at this site would be useful, providing is correlates well to other muscles. To determine the ability of CT to predict IMF%, this study used 400 animals and examined 5 muscles from three sections of the carcass: from the fore-section the m. supraspinatus and m. infraspinatus, from the saddle-section the m. longissimus lumborum and from the hind-section the m. semimembranosus and m. semitendinosus. The average CT pixel density of muscle was negatively associated with IMF% and can be used to predict IMF% although precision in this study was poor. The ability of CT to predict IMF% was greatest in the m. longissimus lumborum (slope −0.07) and smallest in the m. infraspinatus (slope −0.02). The correlation coefficients of IMF% between the five muscles were variable, with the highest correlation coefficients evident between muscles of the fore section (0.67 between the m. supraspinatus and the m. infraspinatus) and the weakest correlations were between the muscle of the fore and hind section. The correlation between the m. longissimus lumborum to the other muscles was fairly consistent with values ranging between 0.34 and 0.40 (partial correlation coefficient). The correlation between the proportion of carcass fat and the IMF% of the five muscles varied and was greatest in the m. longissimus lumborum (0.41).

The aim of this experiment was to study the effects of pen size and parity on maternal behaviour of twin-bearing Small-Tail Han ewes. A total of 24 ewes were allocated to a 2×2 design (six per pen), with parity (primiparous or multiparous) and pen size (large: 6.0×3.0 m; small: 6.0×1.5 m) as main effects at Linyi University, Shandong Province, China. Behaviour was observed from after parturition until weaning. All ewes were observed for 6 h every 5 days from 0700 to1000 h and from 1400 to 1700 h. Continuous focal animal sampling was used to quantify the duration of maternal behaviours: sucking, grooming and following as well as the frequency of udder accepting, udder refusing and low-pitched bleating. Oestradiol and cortisol concentrations in the faeces (collected in the morning every 5 days) were detected using EIA kits. All lambs were weighed 24 h after parturition and again at weaning at 35 days of age. The small pen size significantly reduced following (P<0.005), grooming (P<0.001) and suckling durations (P<0.05), as well as the frequency of udder refusals (P<0.001). However, there was a significant interaction with ewe parity, with decreased grooming and suckling in the small pen largely seen in the multiparous ewes (P<0.001). Independent of pen size, multiparous ewes accepted more sucking attempts by their lambs (P<0.05) and made more low-pitched bleats than primiparous ewes (P<0.001). Multiparous ewes had higher faecal oestradiol concentrations than primiparous ewes (P<0.001), and ewes in small pens had higher faecal cortisol levels compared with ewes in larger pens (P<0.001). As lambs increased in age, the duration of maternal grooming, following and suckling as well as frequency of udder acceptance and low-pitched bleating all declined, and the frequency of udder refusing increased (P<0.001 for all). Ewe parity, but not pen size, affected lamb weight gain during the period of observation (P<0.001). This is the first study to show that pen size, interacting with parity, can affect the expression of maternal behaviour in sheep during lactation. The study is also the first to report on the maternal behaviour of Chinese native sheep breeds (Small-Tail Han sheep), with implications for the production of sheep in China.

In cattle, the detection of very early endometrial responses is considered to be hampered by the presence of only a single embryo. Therefore, we have previously developed a model of multiple embryo transfer to circumvent this hindrance. In this work, we analysed embryo–maternal interactions in the bovine uterus on day 8 of development while comparing the presence of multiple v. single embryos using embryo transfer and artificial insemination, respectively. Concentration of proteins (β-actin, NFkB, clusterin and immunoproteosome 20S β5i subunit–i20S), by western blot, and hexoses (glucose and fructose) were measured in paired samples of uterine fluid (UF) from the same animal with and without embryos in the uterus and were compared with UF obtained after artificial insemination. Prostaglandin (PG) F2 α and PGE2 concentrations were also analysed in blood plasma. The four proteins analysed and hexoses were unaffected by the presence of one or more embryos in the uterus. However, blood PGF2 α showed similar, significant increases with one or more embryos over cyclic animals; such changes were not observed in blood PGE2. Although multiple embryo transfer may appear to be non-physiological, we showed that the uterus, at the very early embryonic stages, does exhibit physiological reactions. Multiple embryo transfer can, therefore, be used for studies of very early embryo–maternal interactions in vivo in monotocous species.

Breeding programmes for livestock require economic weights for traits that reflect the most profitable animal in a given production system, which affect the response in each trait after selection. The profitability of sheep production systems is affected by changes in pasture growth as well as grain, meat and wool prices between seasons and across years. Annual pasture growth varies between regions within Australia’s Mediterranean climate zone from low growth with long periods of drought to high growth with shorter periods of drought. Therefore, the objective of this study was to assess whether breeding objectives need to be adapted for regions, depending on how reliable the pasture growth is across years. We modelled farms with Merino sheep bred for wool and meat in 10 regions in Western Australia. Across these 10 regions, mean annual pasture growth decreased, and the CV of annual pasture growth increased as pasture growth for regions became less reliable. We calculated economic values for nine traits, optimising management across 11 years, including variation for pasture growth and wool, meat and grain prices between and within years from 2002 to 2012. These economic values were used to calculate responses to selection for each trait for the 10 regions. We identified two potential breeding objectives, one for regions with low or high reliability and the other for regions with medium reliability of pasture growth. Breeding objectives for high or low pasture growth reliability had more emphasis on live weight traits and number of lambs weaned. Breeding objectives for medium reliability of pasture growth had more emphasis on decreasing fibre diameter. Relative economic weights for fleece weight did not change across the regions. Regions with low or high pasture reliability had similar breeding objectives and response to selection, because the relationship between the economic values and CV of pasture growth were not linear for live weight traits and the number of lambs weaned. This non-linearity was caused by differences in distribution of pasture growth between regions, particularly during summer and autumn, when ewes were pregnant, with increases in energy requirements affecting the value of lambs weaned. In addition, increasing live weight increased the intake capacity of sheep, which meant that more poor quality pasture could be consumed during summer and autumn, which had more value in regions with low and high pasture reliability. We concluded that breeding values for sheep production systems should be customised depending on the reliability of pasture growth between years.

Bayesian shrinkage analysis estimates all QTLs effects simultaneously, which shrinks the effect of “insignificant” QTLs close to zero so that it does not need special model selection. Bayesian shrinkage estimation usually has an excellent performance on multiple QTLs mapping, but it could not give a probabilistic explanation of how often a QTLs is included in the model, also called posterior inclusion probability, which is important to assess the importance of a QTL. In this research, two methods, FitMix and SimMix, are proposed to approximate the posterior probabilities. Under the assumption of mixture distribution of the estimated QTL effect, FitMix and SimMix mathematically and intuitively fit mixture distribution, respectively. The simulation results showed that both methods gave very reasonable estimates for posterior probabilities. We also applied the two methods to map QTLs for the North American Barley Genome Mapping Project data.

The objective of this work was to study the postmortem evolution of potential biomarkers of autophagy (Beclin 1, LC3-II/LC3-I ratio) and oxidative stress (total antioxidant activity, TAA; superoxide dismutase activity, SOD and catalase activity, CAT) in the Longissimus dorsi muscle of entire male ((Large White×Landrace)×Duroc) pigs subjected to different management treatments that may promote stress, such as mixing unfamiliar animals at the farm and/or during transport and lairage before slaughter. During the rearing period at the farm, five animals were never mixed after the initial formation of the experimental groups (unmixed group at the farm, UF), whereas 10 animals were subjected to a common routine of being mixed with unfamiliar animals (mixed group at the farm, MF). Furthermore, two different treatments were used during the transport and lairage before slaughter: 10 pigs were not mixed (unmixed group during transport and lairage, UTL), whereas five pigs were mixed with unfamiliar animals on the lorry and during lairage (mixed group during transport and lairage, MTL). These mixing treatments were then combined into three pre-slaughter treatments – namely, UF-UTL, MF-UTL and MF-MTL. The results show that MF-UTL and MF-MTL increased significantly the muscle antioxidant defense (TAA, SOD and CAT) at short postmortem times (4 and 8 h; P<0.001), followed by an earlier depletion of the antioxidant activity at 24 h postmortem (P<0.05). We also found that mixing unfamiliar animals, both at the farm and during transport and lairage, triggers postmortem muscle autophagy, which showed an earlier activation (higher expression of Beclin 1 and LC3-II/LC3-I ratio at 4 h postmortem followed by a decreasing pattern of this ratio along first 24 h postmortem) in the muscle tissues of animals from the MF-UTL and MF-MTL groups, as an adaptive strategy of the muscle cells for counteracting induced stress. From these results, we propose that monitoring the evolution of the main biomarkers of autophagy (Beclin 1, LC3-II/LC3-I ratio) and muscle antioxidant defense (TAA, SOD, CAT) in the muscle tissue within the first 24 h postmortem may help the detection of animal stress and its potential effect on the postmortem muscle metabolism.

The objective of the present study was to estimate heritabilities as well as genetic and phenotypic correlations for egg weight, specific gravity, shape index, shell ratio, egg shell strength, egg length, egg width and shell weight in Japanese quail eggs. External egg quality traits were measured on 5864 eggs of 934 female quails from a dam line selected for two generations. Within the Bayesian framework, using Gibbs Sampling algorithm, a multivariate animal model was applied to estimate heritabilities and genetic correlations for external egg quality traits. The heritability estimates for external egg quality traits were moderate to high and ranged from 0.29 to 0.81. The heritability estimates for egg and shell weight of 0.81 and 0.76 were fairly high. The genetic and phenotypic correlations between egg shell strength with specific gravity, shell ratio and shell weight ranging from 0.55 to 0.79 were relatively high. It can be concluded that it is possible to determine egg shell quality using the egg specific gravity values utilizing its high heritability and fairly high positive correlation with most of the egg shell quality traits. As a result, egg specific gravity may be the choice of selection criterion rather than other external egg traits for genetic improvement of egg shell quality in Japanese quails.

The aim of this study was to evaluate the carcass and meat characteristics of eight muscles from bulls with distinct growth paths. A total of 40 Alentejana male calves were allocated to two distinct feeding regimes. In the continuous growth (CG) system, the animals were fed concentrates plus hay and were slaughtered at 18 months of age. On the other hand, in the discontinuous growth (DG) system, the animals were fed hay until 15 months of age; the cattle were then fed the same diet provided to the CG group from 15 to 24 months of age. The DG reduced hot carcass weight, fatness and dressing %, but the proportions of fat, bone and muscle tissues in the leg were not affected. In contrast, there was a positive impact of compensatory growth on supraspinatus, triceps brachii, semitendinosus, biceps femoris muscle tenderness, overcoming the negative effects of age at slaughter. The reasons for such improvement in meat tenderness were not related to intra-muscular fat content or myofibrillar protein degradation values. An association between tenderness and muscle collagen properties was not established. The results indicate that the compensatory growth has a muscle-dependent effect.

Development of mammalian lung involves reiterative outgrowth and branching of an epithelial tube into the surrounding mesenchymal bed. Each coordinated growth and branching cycle is driven by reciprocal signalling between epithelial and adjacent mesenchymal cells. This signalling network includes FGF, SHH, BMP4 and other pathways. We have characterized lung defects in 36Pub mice carrying a deletion that removes an antagonist of FGF signalling, Spry2. Spry2 deficient mice show an enlarged cystic structure located in the terminus of each lobes. Our study shows that Spry2 deficient lungs have reduced lung branching and the cystic structure forms in the early lung development stage. Furthermore, mice carrying a targeted disruption of Spry2 fail to complement the lung phenotype characterized in 36Pub mice. A Spry2-BAC transgene rescues the defect. Interestingly, cystic structure growth is accompanied by the reduced and spatially disorganized expression of Fgf10 and elevated expression of Shh and Bmp4. Altered signalling balance due to the loss of Spry2 causes a delayed branch cycle and cystic growth. Our data underscores the importance of restricting cellular responsiveness to signalling and highlights the interplay between morphogenesis events and spatial localization of gene expression.

Next-generation sequencing (NGS) technologies have played a central role in the genetic revolution. These technologies, especially whole-exome sequencing, have become the primary tool of geneticists to identify the causative DNA variants in Mendelian disorders, including hereditary deafness. Current research estimates that 1% of all human genes have a function in hearing. To date, mutations in over 80 genes have been reported to cause nonsyndromic hearing loss (NSHL). Strikingly, more than a quarter of all known genes related to NSHL were discovered in the past 5 years via NGS technologies. In this article, we review recent developments in the usage of NGS for hereditary deafness, with an emphasis on whole-exome sequencing.

The aims of this study were to estimate the genetic variation of traditional milk coagulation properties (MCPs), milk acidity, curd firmness (CF) modeled on time t (CFt ; comprising: RCTeq, rennet coagulation time estimated from the equation; CFP , the asymptotic potential curd firmness; kCF, the curd firming instant rate constant; and kSR, the syneresis instant rate constant) and maximum CF traits (MCF; comprising CFmax, the maximum CF value; and tmax, the time of attainment). Furthermore, we investigated 96 single nucleotide polymorphisms (SNPs) from 54 candidate genes, testing their associations with the above-listed traits. Milk and blood samples were collected from 1271 cows (each sampled once) from 85 herds. Genotyping was performed using a custom Illumina VeraCode GoldenGate approach. A Bayesian linear animal model (including the effects of herd, days in milk, parity and additive polygenic effects) was used to estimate the genetic parameters of the studied traits. The same model with the addition of the SNP genotype effect was used for our association analysis. The heritability estimates of CFt and the MCF traits (RCTeq=0.258; kCF=0.230; CFmax=0.191; tmax=0.278) were similar to those obtained using traditional MCPs (0.187 to 0.267), except for the lower estimates for CFP (0.064) and kSR (0.077). A total of 13 of the 51 tested SNPs had relevant additive effects on at least one trait. We observed associations between MCPs and SNPs in the genes encoding ATP-binding cassette sub-family G member 2 (ABCG2), chemokine ligand 2 (CCL2), growth hormone 1 (GH1), prolactin (PRL) and toll-like receptor 2 (TLR2). Whereas, CFt and the MCF traits were associated with polymorphisms in the α-s1-casein (CSN1S1), β-casein (CSN2), GH1, oxidized low-density lipoprotein receptor 1 (OLR1), phospholipase C β1 (PLCB1), PRL and signal transducer and activator of transcription 5A (STAT5A) genes.

Background: Paraganglioma syndrome type 1 (PGL1) is a rare autosomal dominant syndrome associated with multiple, overwhelmingly benign, pheochromocytomas and paragangliomas, attributed to SDHD gene mutations. Objective: Clinically and molecularly characterize a family with uncommon malignant phenotype of paragangliomas attributed to two seemingly pathogenic SDHD germline mutations. Materials & methods: The proband presented with large bilateral carotid body tumours and family history of cervical masses in his five siblings. All family members underwent clinical examination, imaging studies (18F-FDG PET/CT) and genotyping of relevant genes. The proband was diagnosed with locally advanced paraganglioma; his hypertensive, otherwise asymptomatic father, had locally advanced pheochromocytoma and his three siblings showed multiple head and neck masses, confirmed to be paragangliomas with local metastasis. All affected patients carried two germline mutations in the SDHD gene; a previously reported nonsense mutation in exon 1 (p.Trp5X) and a novel missense mutation in exon 2 (p.Pro53Leu), highly deleterious by in silico analysis. Allelic loss at the SDHD locus was not shown for any of the analysed tumours. Conclusions: This is a rare case of malignant PGL1 with seemingly double pathogenic mutations in the SDHD gene, highlighting the possibility that the presence of both mutations is associated with the more aggressive phenotype.

The aim of this research was to determine the influence of dietary replacement of n-6 with n-3 polyunsaturated fatty acids on cellular immunity and oxidative stress in the transition period dairy cows. The experiment was conducted on 20 dairy Holstein cows from 3±1 weeks before parturition until the 6th week of lactation. Both groups were fed an iso-energetic and iso-nitrogenous diet. Soybean meal from control (C) group was replaced with linseed in the experimental (LS) group. Cellular immunity and oxidative stress were measured on days −10, 1, 21 and 42 relative to parturition. During the entire experimental period, the proportion of CD45+ cells was lower (P<0.05) in LS group compared with the C group. The phagocytosis ability and phagocytosis index of cows fed with n-3 fatty acids were significantly reduced (P<0.05) compared with the group of cows fed with n-6 fatty acids. The most severe decrease in phagocytosis ability was on day −10 and 1 relative to parturition. The activity of superoxide dismutase (P<0.05) and plasma glutathione peroxidase (P<0.05) increased around calving, although activities were not influenced by dietary treatment. Increased malondialdehyde concentration (P<0.05) was influenced by dietary n-3 fatty acids and the time relative to parturition. The immune suppression was most pronounced during periparturient period. In that matter we can conclude that not only dietary n-3 fatty acids but also oxidative stress, which reached peak at time of parturition, contributed to the reduced cellular immunity during the periparturient period.

Carotenoids are important for human health because of their provitamin A function among other biological actions. Their implication on consumer point of view of cattle products have been widely studied, but very little information is available for horse products. The aim of this study was to study the accumulation of carotenoids, retinoids and tocopherol by HPLC and HPLC-MS analysis in different horse tissues (plasma, milk, adipose tissue and liver) and compare it with that of cattle. Fat color was also studied. Four groups of animals were studied (15 animals within each group): lactating mares (709.82±23.09 kg) and cows (576.93±31.94 kg) reared outdoors; and foals (556.8±25.9 kg, 14 months old) and calves (474.7±36.2 kg, 14 months old) reared indoors. Both mares and foals were from the Hispano–Breton breed, whereas both cows and calves belonged to the commercial crossbred Limousine–Retinta. Differences in plasma and milk carotenoids (P<0.05, P<0.001) were found between mares and cows. Similar levels of vitamin A accumulation in the plasma and fat were detected in foals and calves (P>0.05). Both species showed different levels of accumulation of retinoids in the liver, with the foal having better accumulation (P<0.01, P<0.001). These results indicate that there are species-specific differences in the accumulation of carotenoids, retinol and tocopherol, but further studies are required to establish the mechanism of these differences.

Fasting heat production (FHP) is used for characterizing the basal metabolic rate of animals and the corresponding maintenance energy requirements and in the calculation of net energy value of feeds. In broilers, the most recent FHP estimates were obtained in the 1980s in slow-growing and fatter birds than nowadays. The FHP values (n=73; six experiments) measured in 3 to 6-week-old modern lines of broilers weighing 0.6 to 2.8 kg and growing at 80 to 100 g/day were used to update these literature values. Each measurement was obtained in a group of fasting broilers (5 to 14 birds) kept in a respiration chamber for at least 24 h. The FHP estimate corresponds to the asymptotic heat production corrected for zero physical activity obtained by modeling the decrease in heat production during the fasting day. The compilation of these data indicates that FHP was linearly related to the BW0.70 (in kg), which can be considered as the metabolic BW of modern broilers. The 0.70 exponent differs from the conventional value of 0.75 used for mature animals. The FHP per kg of BW0.70 ranged between 410 and 460 kJ/day according to the experiment (P<0.01). An experiment conducted with a shorter duration of fasting (16 h) indicated that FHP values are higher than those obtained over at least 24 h of fasting. Our values are similar to those obtained previously on fatter and slow-growing birds, even though the comparison is difficult since measurement conditions and methodologies have changed during the last 30 years. The FHP values obtained in our trials represent a basis for energy nutrition of modern broilers.